Sandra Zinkel
Assistant Professor of Medicine
Last active: 3/26/2019

Proapoptotic BID is required for myeloid homeostasis and tumor suppression.

Zinkel SS, Ong CC, Ferguson DO, Iwasaki H, Akashi K, Bronson RT, Kutok JL, Alt FW, Korsmeyer SJ
Genes Dev. 2003 17 (2): 229-39

PMID: 12533511 · PMCID: PMC195974 · DOI:10.1101/gad.1045603

The proper expansion and contraction of hematopoietic cells requires tight regulation of cell death. BID, a "BH3-only" molecule, amplifies death receptor signals connecting the extrinsic to intrinsic pathways by triggering the mitochondrial pathway of apoptosis. Bid-deficient mice, as they age, spontaneously develop a myeloproliferative disorder, which progresses from myeloid hyperplasia to a fatal, clonal malignancy closely resembling chronic myelomonocytic leukemia (CMML). Thus, an apoptotic defect can result in myeloid leukemogenesis. Premalignant Bid-/- myeloid precursor cells are resistant to death receptor-induced apoptosis. Furthermore, a competitive reconstitution assay demonstrates that Bid-deficient long-term repopulating cells give rise to expanded myelomonocytic cells in vivo. Surprisingly, a single BH3-only molecule operating in the extrinsic death receptor pathway proved essential in vivo for physiologic cell death required to maintain myeloid homeostasis. Moreover, progression to CMML indicates that an upstream BH3-only molecule, BID, is required to suppress tumorigenesis.

MeSH Terms (15)

Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Carrier Proteins Chromosome Aberrations Female Homeostasis Leukemia, Myelomonocytic, Chronic Male Mice Mice, Inbred C57BL Mice, Knockout Myelopoiesis Myeloproliferative Disorders Signal Transduction

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